Tissue processing apparatus for processing biological tissue

ABSTRACT

A tissue processing apparatus for processing biological tissue. The tissue processing apparatus comprises a measurement probe that includes two measurement surfaces spaced apart from each other, wherein the measurement probe is configured to be inserted into a reagent receptacle so that the two measurement surfaces are at least partially immersed in reagent contained in the reagent receptacle. The tissue processing apparatus is configured to use the two measurement surfaces of the measurement probe to obtain at least one electrical measurement of reagent contained in the reagent receptacle before reagent is taken out from the reagent receptacle by the tissue processing apparatus. The tissue processing apparatus is configured to determine, based on the at least one electrical measurement, a concentration and/or a type of reagent contained in the reagent receptacle.

FIELD OF THE INVENTION

This invention relates to a tissue processing apparatus for processingbiological tissue.

BACKGROUND

When biological tissue samples are collected, it is common to preparethe samples for analysis, e.g. for viewing under a microscope. Onemethod of preparation is to process the tissue samples by treating thebiological tissue using various fluids and then to embed each sample inan embedding medium, typically a block of paraffin wax. The variousfluids used to treat the samples typically include reagents such as:fixatives, alcohols and hydrocarbon solvents.

Biological tissue is typically processed by a tissue processingapparatus. Prior to processing biological tissue in a tissue processingapparatus, the biological tissue is typically stored in a fixative suchas Formaldehyde. Within a typical tissue processing apparatus,biological tissue is first treated with alcohol, and then with ahydrocarbon solvent, such as Xylene. Finally, the tissue processingapparatus treats the biological tissue with paraffin wax (an embeddingmedium) so as to infiltrate and fill the biological tissue with the wax.It typically takes 14 hours for the tissue processing apparatus tocomplete this process.

Next, the biological tissue is embedded in a block of paraffin wax by atissue embedding apparatus, which may be referred to as an “embeddingcentre”, in which the biological tissue (now filled with wax) is placedin a mould then filled with paraffin wax, which is rapidly cooled toform a solidified block of paraffin wax of predetermined shape and size(determined by the mould) containing the biological tissue. Thepredetermined shape and size of the block is chosen so that thesolidified block is of a suitable shape and size to be used in amicrotome, where the biological tissue can be cut into very fine slicesthat are suitable for use under a microscope.

The present inventors have observed that processing the biologicaltissue with the wrong state and/or type of reagent can cause seriousproblems in the tissue preparation procedure. For example, initiallytreating biological tissue with pure alcohol can cause the biologicaltissue to be damaged. To reduce the likelihood of damaging biologicaltissue, tissue processing apparatuses are normally configured to treatbiological tissue in stages. For the case of alcohol, the concentrationof the alcohol used to treat the biological tissue is gradually reduced,starting from a dilute form and progressing towards a less dilute(purer) form. The aim is to prevent any degradation of the biologicaltissue during the tissue processing procedure that might render thebiological tissue unsuitable for use.

In earlier models of tissue processing apparatus such as the Pathcentre®Enclosed Tissue Processor, a rotary valve system was used which selectedone reagent receptacle from a number of reagent receptacles. In suchmodels, there would typically be 16 to 20 reagent receptacles stored inthe tissue processing apparatus, each of which contained a differentstate and/or type of reagent. The rotary valve system was configured toselect the reagent receptacles in the required order, so as to treat thebiological tissue with increasing strengths of the correct reagent.However, these models of tissue processing apparatuses generallyrequired a technician to expend significant time and effort to ensurethat each reagent receptacle contained the correct state and/or type ofreagent, prior to the contents of that reagent receptacle being used inthe tissue processing apparatus.

A more recent tissue processing apparatus made by Thermo FisherScientific under the name “Shandon Excelsior”, referred to herein as an“Excelsior” tissue processor uses so-called “in-process” reagentmanagement. The Excelsior tissue processor has multiple differentreagent containing reagent receptacles, some of which contain alcohol ofvarying strengths, and others of which contain xylene of varying purity.Unlike the Pathcentre® rotary valve system, the “in-process” reagentmanagement performed by the Excelsior tissue processor only requires theinput of reagent receptacles containing pure alcohol and pure xylene,with other concentrations of alcohol and purity of xylene being obtainedand controlled through use of the apparatus itself.

The Excelsior tissue processor also has a floating buoy mechanism thatis used to obtain specific gravity measurements of alcohol used by thetissue processor. These specific gravity measurements are used to inferthe concentration of reagent in other reagent receptacles so that adetermination can be made on when a new reagent receptacle containingnew reagent is required.

The present inventors have observed a problem with existing tissueprocessing apparatuses in that, when a user is prompted to connect anextraction device of the tissue processing apparatus to a reagentreceptacle containing reagent of a specified type and state (e.g. 100%alcohol, 100% xylene), sometimes the user forgets to perform this actionor accidentally connects the extraction device to a reagent receptaclecontaining reagent that does not match the specified state and/or typeof reagent. If a reagent of a wrong state and/or type is used by thetissue processing apparatus, this can cause irreversible damage to thebiological tissue. However, these problems may not become apparent untilafter the biological tissue has been processed by the apparatus (whichas noted above can take 14 hours).

The present invention has been devised in light of the aboveconsiderations.

SUMMARY OF THE INVENTION

A first aspect of the invention may provide:

-   -   a tissue processing apparatus for processing biological tissue,        the tissue processing apparatus comprising:    -   a measurement probe that includes two measurement surfaces        spaced apart from each other, wherein the measurement probe is        configured to be inserted into a reagent receptacle so that the        two measurement surfaces are at least partially immersed in        reagent contained in the reagent receptacle;    -   wherein the tissue processing apparatus is configured to use the        two measurement surfaces of the measurement probe to obtain at        least one electrical measurement of reagent contained in the        reagent receptacle before reagent is taken out from the reagent        receptacle by the tissue processing apparatus;    -   wherein the tissue processing apparatus is configured to        determine, based on the at least one electrical measurement, a        state and/or a type of reagent contained in the reagent        receptacle.

In this way, the state and/or the type of reagent contained in thereagent receptacle can be determined before reagent is taken out of thereagent receptacle. This allows, for example, the tissue processingapparatus to provide an indication to a user if it is determined thatthe state and/or type of the reagent contained in the reagent receptacledoes not match a specified state and/or type.

The tissue processing apparatus may have an extraction device configuredto take reagent out of the reagent receptacle, when connected to (e.g.inserted into) the reagent receptacle.

The extraction device may be an inlet tube configured to take reagentout of the reagent receptacle via a reagent opening in the inlet tube,when inserted into the reagent receptacle. The reagent opening in theinlet tube may be located at an end of the inlet tube.

Preferably, the measurement probe is mounted to the inlet tube. In thisway, the measurement probe can be assumed to be in the same reagent asthe inlet tube.

Preferably, the measurement probe is mounted to the inlet tube such thatat least part of the measurement probe is located adjacent to thereagent opening in the inlet tube. In this way, the measurement probecan be exposed to reagent similar to the reagent that will be taken outof the reagent receptacle by the inlet tube.

The measurement probe may have a sample chamber, wherein one of the twomeasurement surfaces includes at least one wall of the sample chamber,and the other of the two measurement surfaces is housed within the atleast one wall of the sample chamber. The at least one wall of thesample chamber may be a cylindrical wall. The sample chamber may be openat two (preferably opposite) ends to allow reagent in the reagentreceptacle to pass through the sample chamber.

The inlet tube may have one or more walls which define a compartmentconfigured to house the measurement probe, wherein the one or more wallswhich define the compartment are integrally formed with the remainder ofthe inlet tube.

Preferably, the compartment includes a compartment opening that islocated adjacent to the reagent opening in the inlet tube. Thecompartment preferably includes a further opening which is preferablylocated at an opposite end of the compartment.

Preferably, each measurement surface of the measurement probe iselectrically conductive, and may be a metal such as stainless steel.

The at least one electrical measurement may be indicative of thecapacitance and/or the resistance of the reagent.

Preferably, the tissue processing apparatus includes signal generatingcircuitry configured to generate an electrical test signal that issupplied to at least one of the two measurement surfaces, and signalprocessing circuitry configured to obtain the at least one electricalmeasurement by processing an electrical signal received from at leastone of the two measurement surfaces in consequence of the electricaltest signal having been supplied to at least one of the two measurementsurfaces.

Preferably, the electrical test signal is an AC voltage. The AC voltagemay be a stepped AC signal that oscillates between two or more(preferably three or more) discrete voltages (e.g. as shown in FIG. 6).

Preferably, the signal processing circuitry includes circuitry housed ina cap for use with a reagent receptacle. The cap may be a screw cap.

In this way, at least some of the signal processing circuitry can beprovided reasonably close to the measurement surfaces of the measurementprobe, without requiring that circuitry to be submersed in reagentcontained in the reagent receptacle (which might be impractical). Thishelps to reduce the risk of the electrical signal received from at leastone of the two measurement surfaces getting contaminated in transit tothe signal processing circuitry. Also, a cap is easily transferrablebetween different reagent receptacles whilst remaining connected to thetissue processing apparatus (as may be useful if a reagent receptacleneeds replacing).

A state of reagent determined by the tissue processing apparatus mayinclude a concentration of reagent. The concentration of reagent may beexpressed as a percentage (by volume) of the reagent that is of aspecified type of reagent (e.g. 100% alcohol). For avoidance of anydoubt, the concentration of a reagent may be expressed as a state ofdilution of a reagent.

A type of reagent determined by the tissue processing apparatus mayinclude an indication of whether the reagent is one of a group ofpredetermined reagent types. The predetermined reagent types may includean alcohol, a hydrocarbon solvent and/or a fixative.

As discussed below with reference to FIG. 7, it is fairlystraightforward to determine a concentration of a reagent and anindication of whether the reagent is one of a group of predeterminedreagent types, based on an electrical measurement obtained using twomeasurement surfaces immersed in the reagent. In the example discussedbelow, this is achieved using an electrical measurement indicative ofcapacitance, but the inventors note that other electrical measurementsmay equally be used. The tissue processing apparatus may be configuredto determine a state and/or a type of reagent contained in the reagentreceptacle by comparing the at least one electrical measurement with atleast one reference value. This may be referred to as determining astate and/or a type of reagent based on an “absolute comparison”. The atleast one reference value may be determined empirically (by experiment),for example.

Alternatively, the tissue processing apparatus may be configured todetermine a state and/or type of reagent contained in the reagentreceptacle by comparing the at least one electrical measurement with atleast one electrical measurement previously obtained using themeasurement probe. This may be referred to as determining a state and/ora type of reagent based on an “relative comparison”. The at least oneelectrical measurement previously obtained using the measurement probecould be obtained when the at least two surfaces of the measurementprobe were at least partially immersed in reagent that the tissueprocessing apparatus had deemed as requiring replacement, for example.

Other ways in which the tissue processing apparatus could be configuredto determine, based on the at least one electrical measurement, a stateand/or a type of reagent contained in the reagent receptacle would beapparent to a skilled person.

Preferably, the tissue processing apparatus is configured to:

-   -   provide an indication to a user (e.g. via a display of the        tissue processing apparatus) to connect an extraction device of        the tissue processing apparatus to a reagent receptacle        containing reagent of a specified type and state (e.g. 100%        alcohol, e.g. 100% xylene);    -   after the user has connected the extraction device to a reagent        receptacle:        -   using the two measurement surfaces of the measurement probe            to obtain at least one electrical measurement of reagent            contained in the reagent receptacle before reagent is taken            out from the reagent receptacle by the extraction device;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the reagent receptacle;    -   if the determined state and/or type of reagent contained in the        reagent receptacle does not match the specified state and/or        type, provide an indication to the user that the reagent        contained in the reagent receptacle connected to the extraction        device does not match the specified state and/or type.

The specified type and state of reagent may be a dehydrant having aconcentration of X % or higher, where X is preferably 90% or higher. Forexample, the specified type and state of reagent may be 100% (i.e. pure)alcohol.

The specified type and state of reagent may be a hydrocarbon solventhaving a concentration of X % or higher, where X is preferably 90% orhigher. For example, the specified type and state of reagent may be 100%(i.e. pure) xylene.

Criteria for determining whether the determined state and/or type ofreagent contained in the reagent receptacle does or does not match thespecified state and/or type may involve assessing whether the at leastone electrical measurement falls within at least one predetermined rangecorresponding to the specified state and/or type. The at least onepredetermined range may be determined empirically (by experiment), forexample (see e.g. FIG. 7, discussed below).

Optionally, the tissue processing apparatus may be configured to, if thedetermined state and/or type of reagent contained in the reagentreceptacle connected to the extraction device does not match thespecified state and/or type, prevent the extraction device from takingout reagent from the reagent receptacle, e.g. until the extractiondevice is connected to a reagent receptacle containing reagent that isdetermined to have a state and/or type that matches the specified stateand/or type; and/or until a predetermined override procedure is carriedout by a user of the tissue processing apparatus.

Reagent contained in a reagent receptacle may be one of: an alcohol, ahydrocarbon solvent or a fixative.

Preferably, the tissue processing apparatus is for processing biologicaltissue by treating the biologicial tissue with a plurality of reagentsand then with an embedding medium. The plurality of reagents used toprocess the biological tissue may include one or more (preferably aplurality of) dehydrants and one or more (preferably a plurality of)hydrocarbon solvents. The one or more dehydrants may include a pluralityof alcohol solutions having differing concentrations and/or purealcohol. The one or more hydrocarbon solvents may include one or morexylene solutions and/or pure xylene. The embedding medium may beparaffin wax.

The tissue processing apparatus may include a control unit forcontrolling operation of the tissue processing apparatus. The controlunit may be configured to carry out one or more of the above-describeddetermination steps and/or provide one or more of the above-describedindications to a user.

An above-described indication to a user may be provided, for example,via a display of the tissue processing apparatus, via a mobile phoneapplication and/or via a message sent to a mobile phone. Other modes ofproviding information to a user could easily be envisaged by a skilledperson.

The tissue processing apparatus may have a display, though this is not arequirement since indications to a user may be provided by means otherthan a display (as can be seen from the previous paragraph). The displaycould be wirelessly connected to the tissue processing apparatus (e.g.it could be a remote PC).

The tissue processing apparatus may include a cavity for housing one ormore reagent receptacles.

The tissue processing apparatus may include multiple measurement probes.In this way, the tissue processing apparatus can be used to check thestate and/or type of reagent contained in multiple reagent receptacles.

Each measurement probe may be as described in connection with a singlemeasurement probe, above.

Preferably, the tissue processing apparatus includes first and secondmeasurement probes, wherein the first measurement probe is configured tobe inserted into a first reagent receptacle and the second measurementprobe is configured to be inserted into a second reagent receptacle.

Preferably, the tissue processing apparatus is configured to:

-   -   provide an indication to a user to connect a first extraction        device of the tissue processing apparatus to a first reagent        receptacle containing reagent of a first specified type and        state (e.g. 100% alcohol);    -   after the user has connected the first extraction device to a        first reagent receptacle:        -   using the two measurement surfaces of a first measurement            probe to obtain at least one electrical measurement of            reagent contained in the first reagent receptacle before            reagent is taken out from the first reagent receptacle by            the first extraction device;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the first reagent receptacle;    -   if the determined state and/or type of reagent contained in the        first reagent receptacle does not match the first specified        state and/or type, provide an indication to the user that the        reagent contained in the first reagent receptacle does not match        the first specified state and/or type;    -   provide an indication to a user to connect a second extraction        device of the tissue processing apparatus to a second reagent        receptacle containing reagent of a second specified type and        state (e.g. 100% xylene);    -   after the user has connected the second extraction device to a        second reagent receptacle:        -   using the two measurement surfaces of the second measurement            probe to obtain at least one electrical measurement of            reagent contained in the second reagent receptacle before            reagent is taken out from the second reagent receptacle by            the second extraction device;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the second reagent receptacle;    -   if the determined state and/or type of reagent contained in the        second reagent receptacle does not match the second specified        type and/or state, provide an indication to the user that the        reagent contained in the second reagent receptacle does not        match the second specified state and/or type.

The first extraction device is preferably a first inlet tube of thetissue processing apparatus to which the first measurement probe ismounted, and the second extraction device is preferably a second inlettube of the tissue processing apparatus to which the second measurementprobe is mounted.

The first specified type and state of reagent may be a dehydrant havinga concentration of X % or higher, where X is preferably 90% or higher.For example, the first specified type and state of reagent may be 100%alcohol.

The second specified type and state of reagent may be a hydrocarbonsolvent having a concentration of X % or higher, where X is preferably90% or higher. For example, the second specified type and state ofreagent may be 100% xylene.

A second aspect of the invention may provide a method of using a tissueprocessing apparatus according to the first aspect of the invention.

The second aspect of the invention may therefore provide a method ofusing a tissue processing apparatus according to the first aspect of theinvention, wherein the method includes:

-   -   inserting the measurement probe into a reagent receptacle        containing reagent so that the two measurement surfaces of the        measurement probe are at least partially immersed in reagent        contained in the reagent receptacle;    -   using the two measurement surfaces of the measurement probe to        obtain at least one electrical measurement of reagent contained        in the reagent receptacle before reagent is taken out from the        reagent receptacle by (e.g. an extraction device of) the tissue        processing apparatus;    -   determining, based on the at least one electrical measurement, a        state and/or a type of the reagent contained in the reagent        receptacle.

The method may include any method step implementing or corresponding toany apparatus feature described in connection with the first aspect ofthe invention.

A third aspect of the invention may provide a measurement probeconfigured to be used in a tissue processing apparatus according to thefirst aspect of the invention.

The measurement probe may have any feature described in connection withany above aspect of the invention.

For example, the measurement probe may be provided in combination withan inlet tube and/or reagent receptacle cap as described in connectionwith any above aspect of the invention.

The invention also includes any combination of the aspects and preferredfeatures described except where such a combination is clearlyimpermissible or expressly avoided.

BRIEF DESCRIPTION OF THE DRAWINGS

Examples of these proposals are discussed below, with reference to theaccompanying drawings in which:

FIG. 1 is an example tissue processing apparatus.

FIG. 2 is a cross-sectional view of a first example of a reagentreceptacle suitable for use in the tissue processing apparatus ofFIG. 1. The reagent receptacle has a first example of a measurementprobe inserted into it.

FIG. 3 is a cross-sectional view of the first example of the measurementprobe.

FIG. 4 is a schematic diagram of a second example of the measurementprobe suitable for use in the tissue processing apparatus of FIG. 1.

FIG. 5 is an exploded diagram of the measurement probe of FIG. 4.

FIG. 6 is a graph showing an example stepped AC waveform that could beused as an electrical test signal.

FIG. 7 is a bar chart showing capacitance measurements obtained forreagents having various different states and types.

DETAILED DESCRIPTION

In general, the following discussion describes examples of our proposalswith reference to the exemplary embodiments displayed in the figures.

FIG. 1 illustrates an example of a tissue processing apparatus 100according to the present invention.

The tissue processing apparatus 100 has a first extraction device in theform of a first inlet tube 110 a configured to take reagent out of afirst reagent receptacle 120 a via a reagent opening located at an endof the first inlet tube 110 a, when inserted into the first reagentreceptacle 120 a. The tissue processing apparatus 100 also has a secondextraction device in the form of a second inlet tube 110 b configured totake reagent out of a second reagent receptacle 120 b via a reagentopening located at an end of the second inlet tube 110 b, when insertedinto the second reagent receptacle 120 b.

The reagent receptacles 120 a, 120 b would typically be housed within acavity inside the tissue processing apparatus 100, but in FIG. 1 theyare shown externally to the tissue processing apparatus 100 for clarity.

The tissue processing apparatus 100 also includes a control unit 130(e.g. a computer), a display 135 and signal generating circuitry 140.

FIG. 2 shows an inlet tube 210, a reagent receptacle 220 and a firstexample of a measurement probe 250 suitable for use in the tissueprocessing apparatus of FIG. 1, wherein the inlet tube 210 houses themeasurement probe 250. The measurement probe 250 is only shown partiallyin FIG. 2, but a more detailed view of the measurement probe 250 isprovided by FIG. 3, discussed in more detail below.

In this example, signal processing circuitry 230 of the tissueprocessing apparatus 100 is housed within a cap 225 of the reagentreceptacle 220. The signal processing circuitry 230 is connected to thecontrol unit 130 of the signal processing apparatus 100 via a connectingcable, which is omitted from FIG. 2 for clarity. The function of thesignal processing circuitry 230 housed within the cap 225 is describedbelow.

FIG. 3 shows the measurement probe 250 and inlet tube 210 of FIG. 2 inmore detail. The inlet tube 210 has a reagent opening 205 located at theend of the inlet tube 210, through which the inlet tube 210 isconfigured to take reagent out of the reagent receptacle 220. The inlettube 210 has an internal wall which defines a compartment 215 configuredto house the measurement probe 250. The internal wall of the inlet tube210 is integrally formed with the remainder of the inlet tube 210. Thecompartment 215 includes a compartment opening 216 located adjacent tothe reagent opening 205. The compartment opening 216 is formed in ameasurement end cap 292 (described below). The compartment 215 iscylindrical and also includes a further compartment opening 217, whichis located at the opposite end of the compartment 215 to the compartmentopening 216, so as to allow reagent to flow through the compartment 215and the measurement probe 250. At the same end of the compartment 215 asthe further compartment opening 217, there is a small hole (unlabelled)to allow the coaxial cable 282 (described below) to pass into thecompartment 215.

A standard inlet tube for a reagent receptacle of the type used intissue processing apparatuses is typically 12 mm to 13 mm in diameter.In contrast, the combination of the measurement probe 250 and the inlettube 210 shown in FIG. 3 may have a width of between 27 and 30 mm, whichis still narrow enough to be inserted into the hole of a standard sizedbottle typically used as a reagent receptacle in a tissue processingapparatus.

The measurement probe 250 includes first and second measurement surfaces261, 262. The first measurement surface 261 is a cylindrical wall thatdefines a sample chamber that is open at opposite ends to allow reagentin the reagent receptacle 220 to pass through the sample chamber. Thesecond measurement surface 262 is an elongate element housed coaxiallywithin the cylindrical wall provided by the first measurement surface261.

An input cable 270 electrically connects the signal generating circuitry140 of the tissue processing apparatus to the second measurement surface262. The input cable 270 is attached (in this example by soldering) tothe second measurement surface 262 within a heat shrink 275. The firstmeasurement surface 261 is connected to the signal processing unit(provided by the circuitry 230) by a return cable 280, which iselectrically connected to the first measurement surface 261 by a returnclamp 285. The input cable 270 and return cable 280 together formrespective parts of a coaxial cable 282 which connects back to thetissue processing apparatus 100.

The input cable 270 enters the sample chamber at a cable end of thesample chamber, where it is secured in place by a cable end cap 291.Likewise, the second measurement surface 262 is secured in place at ameasurement end of the sample chamber by a measurement end cap 292. Themeasurement end cap 292 is configured to secure the second measurementsurface 262 so as to be spaced apart from the first measurement surface261, with the first measurement surface 261 and the second measurementsurface 262 being coaxial with each other.

In use, the tissue processing apparatus 100 provides an indication to auser (e.g. via the display 135, via a mobile phone application, and/orvia a message sent to a mobile phone belonging to the user) to connectthe inlet tube 210 (which for the purposes of this example may forexample be the first inlet tube 110 a or the second inlet tube 110 b) toa reagent receptacle containing reagent of a specified type and state(e.g. 100% alcohol). After the user has connected the inlet tube 210 tothe reagent receptacle 220 (which may for the purposes of this examplemay be the first reagent receptacle 120 a or the second reagentreceptacle 120 b) by inserting the inlet tube 210 into the reagentreceptacle 220 so that the two measurement surfaces 261, 262 are atleast partially immersed in reagent contained in the reagent receptacle220, the tissue processing apparatus 100 uses the two measurementsurfaces 261, 262 of the measurement probe 250 to obtain at least oneelectrical measurement of the reagent contained in the reagentreceptacle 220.

To obtain the at least one electrical measurement of the reagentcontained in the reagent receptacle 220, the signal generating circuitry140 generates an electrical test signal, which is supplied to the secondmeasurement surface 262 via the input cable 270. An electrical signalreceived from the first measurement surface 261 in consequence of theelectrical test signal having been supplied to the second measurementsurface 262 (caused by capacitive coupling of the first and secondmeasurement surfaces 261, 262) is then received by and processed by thesignal processing circuitry 230 to provide at least one electricalmeasurement, which is relayed to the control unit 130.

In this example, the at least one electrical measurement is indicativeof the capacitance of the reagent contained in the reagent receptacle220.

Equally, it would be possible for the at least one electricalmeasurement to be indicative of the capacitance and resistance of thereagent contained in the reagent receptacle 220, or to be indicative ofjust the resistance of the reagent.

In some embodiments, either/both of the first and second measurementsurfaces 261, 262 may have a layer of electrical insulation formedthereon, but in this case it would not be possible to use the first andsecond measurement surfaces 261, 262 to obtain an electrical measurementindicative of the resistance of the reagent.

Next, the tissue processing apparatus 100 determines, based on theelectrical measurement indicative of the capacitance of the reagentcontained in the reagent receptacle 220, a state and a type of reagentcontained in the reagent receptacle 220 by comparing the electricalmeasurement with at least one reference value (based on an “absolutecomparison”). The at least one reference value may be determinedempirically, e.g. as discussed below with reference to FIG. 7.

Next, if the determined state and/or type of reagent contained in thereagent receptacle 220 does not match the specified state and/or type(e.g. within a predetermined threshold), the tissue processing apparatus100 provides an indication to the user, via the display 135, that thereagent contained in the reagent receptacle 220 does not match thespecified state and/or type.

Optionally, the tissue processing apparatus 100 may be configured to, ifthe determined state and/or type of reagent contained in the reagentreceptacle 220 does not match the specified state and/or type, preventthe inlet tube 210 from taking out reagent from the reagent receptacle220, e.g. until the inlet tube 210 is inserted into a reagent receptaclecontaining reagent that is determined to have a state and/or type thatmatches the specified state and/or type; and/or until a predeterminedoverride procedure is carried out by a user of the tissue processingapparatus 100.

In this way, if the inlet tube 210 is inserted into a reagent receptaclecontaining reagent that does not match the specified state and/or type,then the tissue processing apparatus 100 can be prevented from usingthat reagent.

FIG. 4 and FIG. 5 show a second example of a measurement probe 350suitable for use in the tissue processing apparatus 100 of FIG. 1.Corresponding reference numerals have been used for correspondingfeatures which have previously been described. Such features aretherefore only described to the extent that they deviate significantlyfrom the measurement probe shown in FIGS. 2 and 3.

The measurement probe 350 shown in FIGS. 4 and 5 has essentially thesame structure as the measurement probe 250 of FIGS. 2 and 3, and couldbe used in the tissue processing apparatus of FIG. 1 in much the sameway as the the measurement probe 250 of FIGS. 2 and 3.

Where the measurement probe 350 shown in FIGS. 4 and 5 differs from themeasurement probe 250 of FIGS. 2 and 3 is in the mounting of themeasurement probe 350 to the inlet tube 310. In particular, themeasurement probe 350 shown in FIGS. 4 and 5 is mounted to the inlettube 310 via a probe attachment clip 345. A cable attachment clip 315attaches the input cable 370 to the inlet tube 310 at a location betweenthe measurement probe 350 and the cap 325. Also illustrated in FIG. 4 isa connecting cable 331, which connects the circuitry 330 to the controlunit 130 of the tissue processing apparatus.

FIG. 5 shows an exploded view of the measurement probe 350 illustratedin FIG. 4.

As shown in FIG. 5, a ground ring 335 is disposed between the firstmeasurement surface 361 and the cable end cap 391 of the measurementprobe 350. The ground ring 335 is connected to a ground wire 340. Thecombination is configured to ensure that the measurement probe issuitably grounded, so as to improve the accuracy of the electricalmeasurements obtained.

FIG. 6 illustrates an example waveform for an electrical test signalthat could be generated by the signal generating circuitry 140. Theillustrated test signal is a 16 kHz stepped AC voltage waveform thatoscillates between three discrete voltages with a peak to peak voltageof 2.5V. The use of such a stepped waveform for the electrical testsignal makes it easier to identify the shift in the phase/amplitude ofthe resulting electrical signal, and therefore obtain electricalmeasurements indicative of capacitance and resistance of a reagent.Other AC voltage waveforms may be used. Whilst it is conceivable that aDC voltage could also be used, testing has shown that this does notalways produce satisfactory results when working with Hydrocarbonsolvents.

FIG. 7 is a bar chart showing capacitance measurements obtained forreagents having various different states and types.

In particular, FIG. 7 shows capacitance measurements, obtained using themeasurement probe 250 of FIGS. 2 and 3, when immersed in reagents havingvarious states and types that might be used in a tissue processingapparatus. The capacitances of the reagents having different states andtypes are shown to be distinct, and thus FIG. 7 demonstrates that thestate and/or type of the reagent can be determined based on acapacitance measurement obtained using the measurement probe 250 ofFIGS. 2 and 3.

When used in this specification and claims, the terms “comprises” and“comprising”, “including” and variations thereof mean that the specifiedfeatures, steps or integers are included. The terms are not to beinterpreted to exclude the possibility of other features, steps orintegers being present.

The features disclosed in the foregoing description, or in the followingclaims, or in the accompanying drawings, expressed in their specificforms or in terms of a means for performing the disclosed function, or amethod or process for obtaining the disclosed results, as appropriate,may, separately, or in any combination of such features, be utilised forrealising the invention in diverse forms thereof.

While the invention has been described in conjunction with the exemplaryembodiments described above, many equivalent modifications andvariations will be apparent to those skilled in the art when given thisdisclosure. Accordingly, the exemplary embodiments of the invention setforth above are considered to be illustrative and not limiting. Variouschanges to the described embodiments may be made without departing fromthe spirit and scope of the invention.

For the avoidance of any doubt, any theoretical explanations providedherein are provided for the purposes of improving the understanding of areader. The inventors do not wish to be bound by any of thesetheoretical explanations.

All references referred to above are hereby incorporated by reference.

The following statements, which are not claims, provide generalexpressions of the disclosure herein.

A1. A tissue processing apparatus for processing biological tissue, thetissue processing apparatus comprising:

-   -   a measurement probe that includes two measurement surfaces        spaced apart from each other, wherein the measurement probe is        configured to be inserted into a reagent receptacle so that the        two measurement surfaces are at least partially immersed in        reagent contained in the reagent receptacle;    -   wherein the tissue processing apparatus is configured to use the        two measurement surfaces of the measurement probe to obtain at        least one electrical measurement of reagent contained in the        reagent receptacle before reagent is taken out from the reagent        receptacle by the tissue processing apparatus;    -   wherein the tissue processing apparatus is configured to        determine, based on the at least one electrical measurement, a        state and/or a type of reagent contained in the reagent        receptacle.

A2. A tissue processing apparatus according to statement A1 having anextraction device configured to take reagent out of the reagentreceptacle, when connected to the reagent receptacle.

A3. A tissue processing apparatus according to statement A2, wherein theextraction device is an inlet tube configured to take reagent out of thereagent receptacle via a reagent opening in the inlet tube, wheninserted into the reagent receptacle.

A4. A tissue processing apparatus according to statement A3, wherein themeasurement probe is mounted to the inlet tube.

A5. A tissue processing apparatus according to statement A4, wherein themeasurement probe is mounted to the inlet tube such that at least partof the measurement probe is located adjacent to the reagent opening inthe inlet tube.

A6. A tissue processing apparatus according to statement A4 or A5,wherein the inlet tube has one or more walls which define a compartmentconfigured to house the measurement probe.

A7. A tissue processing apparatus according to statement A6, wherein theone or more walls which define the compartment are formed integrallywith the remainder of the inlet tube.

A8. A tissue processing apparatus according to any preceding statement,wherein the measurement probe has a sample chamber and wherein one ofthe two measurement surfaces includes at least one wall of the samplechamber.

A9. A tissue processing apparatus according to any preceding statement,wherein the tissue processing apparatus includes signal generatingcircuitry configured to generate an electrical test signal that issupplied to at least one of the two measurement surfaces, and signalprocessing circuitry configured to obtain the at least one electricalmeasurement by processing an electrical signal received from at leastone of the two measurement surfaces in consequence of the electricaltest signal having been supplied to at least one of the two measurementsurfaces.

A10. A tissue processing apparatus according to statement A9, whereinthe signal processing circuitry includes circuitry housed in a cap foruse with a reagent receptacle.

A11. A tissue processing apparatus according to any preceding statement,wherein the tissue processing apparatus is configured to:

-   -   provide an indication to a user to connect an extraction device        of the tissue processing apparatus to a reagent receptacle        containing reagent of a specified type and state;    -   after the user has connected the extraction device to a reagent        receptacle:        -   using the two measurement surfaces of the measurement probe            to obtain at least one electrical measurement of reagent            contained in the reagent receptacle before reagent is taken            out from the reagent receptacle by the extraction device;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the reagent receptacle;    -   if the determined state and/or type of reagent contained in the        reagent receptacle does not match the specified state and/or        type, provide an indication to the user that the reagent        contained in the reagent receptacle connected to the extraction        device does not match the specified state and/or type.

A12. A tissue processing apparatus according to statement A11, whereinthe specified type and state of reagent is a dehydrant having aconcentration of 90% or higher, or a hydrocarbon solvent having aconcentration of 90% or higher.

A13. A tissue processing apparatus according to any preceding statement,wherein the tissue processing apparatus includes first and secondmeasurement probes, wherein the first measurement probe is mounted to afirst inlet tube of the tissue processing apparatus and configured to beinserted into a first reagent receptacle, wherein the second measurementprobe is mounted to a second inlet tube of the tissue processingapparatus and configured to be inserted into a second reagentreceptacle, wherein the tissue processing apparatus is configured to:

-   -   provide an indication to a user to connect the first inlet tube        of the tissue processing apparatus to a first reagent receptacle        containing reagent of a first specified type and state;    -   after the user has inserted the first inlet tube into a first        reagent receptacle:        -   using the two measurement surfaces of the first measurement            probe to obtain at least one electrical measurement of            reagent contained in the first reagent receptacle before            reagent is taken out from the first reagent receptacle by            the first inlet tube;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the first reagent receptacle;    -   if the determined state and/or type of reagent contained in the        first reagent receptacle does not match the first specified        state and/or type, provide an indication to the user that the        reagent contained in the first reagent receptacle does not match        the first specified state and/or type;    -   provide an indication to a user to connect the second inlet tube        of the tissue processing apparatus to a second reagent        receptacle containing reagent of a second specified type and        state;    -   after the user has inserted the second inlet tube into a second        reagent receptacle:        -   using the two measurement surfaces of the second measurement            probe to obtain at least one electrical measurement of            reagent contained in the second reagent receptacle before            reagent is taken out from the second reagent receptacle by            the second inlet tube;        -   determining, based on the at least one electrical            measurement, a state and/or a type of reagent contained in            the second reagent receptacle;    -   if the determined state and/or type of reagent contained in the        second reagent receptacle does not match the second specified        type and/or state, provide an indication to the user that the        reagent contained in the second reagent receptacle does not        match the second specified state and/or type.

A14. A tissue processing apparatus according to statement A13, wherein:

-   -   the first specified type and state of reagent is a dehydrant        having a concentration of 90% or higher;    -   the second specified type and state of reagent is a hydrocarbon        solvent having a concentration of 90% or higher.

A15. A method of using a tissue processing apparatus according to thefirst aspect of the invention, wherein the method includes:

-   -   inserting the measurement probe into a reagent receptacle        containing reagent so that the two measurement surfaces of the        measurement probe are at least partially immersed in reagent        contained in the reagent receptacle;    -   using the two measurement surfaces of the measurement probe to        obtain at least one electrical measurement of reagent contained        in the reagent receptacle before reagent is taken out from the        reagent receptacle by the tissue processing apparatus;    -   determining, based on the at least one electrical measurement, a        state and/or a type of the reagent contained in the reagent        receptacle.

A16. A measurement probe configured to be used in a tissue processingapparatus according to one of statements A1 to A14.

A17. A tissue processing apparatus substantially as any one embodimentherein described with reference to and as shown in the accompanyingdrawings.

1-15. (canceled)
 16. A tissue processing apparatus for processingbiological tissue, the tissue processing apparatus comprising: ameasurement probe that includes two measurement surfaces spaced apartfrom each other, wherein the measurement probe is configured to beinserted into a reagent receptacle so that the two measurement surfacesare at least partially immersed in reagent contained in the reagentreceptacle; wherein the tissue processing apparatus is configured to usethe two measurement surfaces of the measurement probe to obtain at leastone electrical measurement of reagent contained in the reagentreceptacle before reagent is taken out from the reagent receptacle bythe tissue processing apparatus; wherein the tissue processing apparatusis configured to determine, based on the at least one electricalmeasurement, a concentration and/or a type of reagent contained in thereagent receptacle.
 17. A tissue processing apparatus according to claim1, wherein the tissue processing apparatus is configured to: provide anindication to a user to connect an extraction device of the tissueprocessing apparatus to a reagent receptacle containing reagent of aspecified type and concentration; after the user has connected theextraction device to a reagent receptacle: using the two measurementsurfaces of the measurement probe to obtain at least one electricalmeasurement of reagent contained in the reagent receptacle beforereagent is taken out from the reagent receptacle by the extractiondevice; determining, based on the at least one electrical measurement, aconcentration and/or a type of reagent contained in the reagentreceptacle; and if the determined concentration and/or type of reagentcontained in the reagent receptacle does not match the specifiedconcentration and/or type, provide an indication to the user that thereagent contained in the reagent receptacle connected to the extractiondevice does not match the specified concentration and/or type.
 18. Atissue processing apparatus according to claim 2, wherein the specifiedtype and concentration of reagent is a dehydrant having a concentrationof 90% or higher, or a hydrocarbon solvent having a concentration of 90%or higher.
 19. A tissue processing apparatus according to claim 1,wherein the tissue processing apparatus includes first and secondmeasurement probes, wherein the first measurement probe is mounted to afirst inlet tube of the tissue processing apparatus and configured to beinserted into a first reagent receptacle, wherein the second measurementprobe is mounted to a second inlet tube of the tissue processingapparatus and configured to be inserted into a second reagentreceptacle, wherein the tissue processing apparatus is configured to:provide an indication to a user to connect the first inlet tube of thetissue processing apparatus to a first reagent receptacle containingreagent of a first specified type and concentration; after the user hasinserted the first inlet tube into a first reagent receptacle: using thetwo measurement surfaces of the first measurement probe to obtain atleast one electrical measurement of reagent contained in the firstreagent receptacle before reagent is taken out from the first reagentreceptacle by the first inlet tube; determining, based on the at leastone electrical measurement, a concentration and/or a type of reagentcontained in the first reagent receptacle; if the determinedconcentration and/or type of reagent contained in the first reagentreceptacle does not match the first specified concentration and/or type,provide an indication to the user that the reagent contained in thefirst reagent receptacle does not match the first specifiedconcentration and/or type; provide an indication to a user to connectthe second inlet tube of the tissue processing apparatus to a secondreagent receptacle containing reagent of a second specified type andconcentration; after the user has inserted the second inlet tube into asecond reagent receptacle: using the two measurement surfaces of thesecond measurement probe to obtain at least one electrical measurementof reagent contained in the second reagent receptacle before reagent istaken out from the second reagent receptacle by the second inlet tube;determining, based on the at least one electrical measurement, aconcentration and/or a type of reagent contained in the second reagentreceptacle; if the determined concentration and/or type of reagentcontained in the second reagent receptacle does not match the secondspecified type and/or concentration, provide an indication to the userthat the reagent contained in the second reagent receptacle does notmatch the second specified concentration and/or type.
 20. A tissueprocessing apparatus according to claim 4, wherein: the first specifiedtype and concentration of reagent is a dehydrant having a concentrationof 90% or higher; the second specified type and concentration of reagentis a hydrocarbon solvent having a concentration of 90% or higher.
 21. Atissue processing apparatus according to claim 1 having an extractiondevice configured to take reagent out of the reagent receptacle, whenconnected to the reagent receptacle.
 22. A tissue processing apparatusaccording to claim 6, wherein the extraction device is an inlet tubeconfigured to take reagent out of the reagent receptacle via a reagentopening in the inlet tube, when inserted into the reagent receptacle.23. A tissue processing apparatus according to claim 7, wherein themeasurement probe is mounted to the inlet tube.
 24. A tissue processingapparatus according to claim 8, wherein the measurement probe is mountedto the inlet tube such that at least part of the measurement probe islocated adjacent to the reagent opening in the inlet tube.
 25. A tissueprocessing apparatus according to claim 8, wherein the inlet tube hasone or more walls which define a compartment configured to house themeasurement probe.
 26. A tissue processing apparatus according to claim10, wherein the one or more walls which define the compartment areformed integrally with the remainder of the inlet tube.
 27. A tissueprocessing apparatus according to claim 1, wherein the measurement probehas a sample chamber and wherein one of the two measurement surfacesincludes at least one wall of the sample chamber.
 28. A tissueprocessing apparatus according to claim 1, wherein the tissue processingapparatus includes signal generating circuitry configured to generate anelectrical test signal that is supplied to at least one of the twomeasurement surfaces, and signal processing circuitry configured toobtain the at least one electrical measurement by processing anelectrical signal received from at least one of the two measurementsurfaces in consequence of the electrical test signal having beensupplied to at least one of the two measurement surfaces.
 29. A tissueprocessing apparatus according to claim 13, wherein the signalprocessing circuitry includes circuitry housed in a cap for use with areagent receptacle.
 30. A method of using a tissue processing apparatusaccording to claim 1, wherein the method includes: inserting themeasurement probe into a reagent receptacle containing reagent so thatthe two measurement surfaces of the measurement probe are at leastpartially immersed in reagent contained in the reagent receptacle; usingthe two measurement surfaces of the measurement probe to obtain at leastone electrical measurement of reagent contained in the reagentreceptacle before reagent is taken out from the reagent receptacle bythe tissue processing apparatus; determining, based on the at least oneelectrical measurement, a concentration and/or a type of the reagentcontained in the reagent receptacle.